Amino acid replacements MCQs With Answer

Amino acid replacements MCQs With Answer

Introduction: This quiz set helps M.Pharm students deepen their understanding of amino acid replacements and their consequences for protein structure, stability, and formulation. Questions focus on biochemical principles—side chain properties, secondary-structure propensity, disulfide bonds, deamidation, oxidation, proteolytic cleavage, glycosylation motifs—and practical formulation strategies to mitigate degradation (pH control, antioxidants, excipients). Expect items on rational substitution choices (conservative vs non-conservative), alanine scanning, and the impact of single-residue changes on aggregation, immunogenicity, and pharmacokinetics. These MCQs are designed to reinforce theoretical knowledge and to sharpen decision-making skills for protein engineering and formulation optimization in pharmaceutical practice.

Q1. Which substitution is most commonly used in alanine scanning to assess the functional importance of a residue without introducing new side-chain interactions?

• Glycine substitution
• Serine substitution
• Alanine substitution
• Valine substitution

Correct Answer: Alanine substitution

Q2. Replacement of methionine with which residue is often chosen to reduce susceptibility to oxidative degradation while maintaining hydrophobic character?

• Leucine
• Serine
• Proline
• Lysine

Correct Answer: Leucine

Q3. Which replacement is most likely to eliminate an N-linked glycosylation site (consensus sequence N‑X‑S/T) without majorly perturbing backbone conformation?

• Asn to Gln
• Asn to Asp
• Thr to Ser
• Asn to Lys

Correct Answer: Asn to Gln

Q4. Substituting a surface-exposed bulky hydrophobic residue with a charged residue is primarily intended to reduce which formulation problem?

• Protease cleavage
• Aggregation
• Disulfide scrambling
• Glycosylation heterogeneity

Correct Answer: Aggregation

Q5. Which amino acid replacement is commonly used to remove a free cysteine that causes incorrect inter‑ or intramolecular disulfide linkages while minimally altering polarity?

• Cysteine to Serine
• Cysteine to Phenylalanine
• Cysteine to Arginine
• Cysteine to Proline

Correct Answer: Cysteine to Serine

Q6. Introducing a proline residue into a loop region most directly stabilizes a protein by affecting which parameter?

• Reducing loop conformational entropy
• Increasing hydrogen bond donors
• Raising net positive charge
• Creating new glycosylation sites

Correct Answer: Reducing loop conformational entropy

Q7. Which substitution would be most appropriate to prevent deamidation at an Asn position prone to conversion to Asp during storage?

• Asn to Gln
• Asn to Asp
• Asn to Ser
• Asn to Lys

Correct Answer: Asn to Gln

Q8. Replacement of an internal glycine in a tight turn with which residue is most likely to disrupt folding because of steric clash?

• Alanine
• Valine
• Proline
• Glu

Correct Answer: Valine

Q9. Which pair of substitutions is considered conservative because both maintain a similar charge at physiological pH?

• Lysine to Glutamate
• Aspartate to Glutamate
• Tyrosine to Tryptophan
• Serine to Phenylalanine

Correct Answer: Aspartate to Glutamate

Q10. To reduce proteolytic cleavage at a susceptible Lys-Arg site, which strategic substitution is often employed without introducing a charged residue that could create a new cleavage site?

• Lys to Arg
• Lys to Pro
• Lys to Glu
• Lys to Ser

Correct Answer: Lys to Pro

Q11. Which replacement is most likely to affect a salt bridge that stabilizes tertiary structure?

• Leu to Ile
• Asp to Asn
• Phe to Tyr
• Gly to Ala

Correct Answer: Asp to Asn

Q12. Substituting tyrosine with phenylalanine removes which chemical functionality that can influence activity or post‑translational modification?

• Hydroxyl group
• Amino group
• Sulfhydryl group
• Carboxyl group

Correct Answer: Hydroxyl group

Q13. Which substitution is most likely to increase the isoelectric point (pI) of a protein if introduced at multiple surface positions?

• Aspartate to Asparagine
• Glutamate to Lysine
• Serine to Threonine
• Tryptophan to Tyrosine

Correct Answer: Glutamate to Lysine

Q14. When designing a therapeutic protein to reduce immunogenic epitopes, what type of substitution is typically considered to reduce T‑cell recognition while preserving function?

• Non-conservative substitution with bulky aromatic residue
• Conservative substitution guided by sequence homology to human proteins
• Random mutagenesis across the entire protein
• Introducing multiple charged residues in active site

Correct Answer: Conservative substitution guided by sequence homology to human proteins

Q15. Which replacement is a common strategy to prevent methionine oxidation in formulations where oxidative stress is difficult to control?

• Methionine to Isoleucine
• Methionine to Serine
• Methionine to Arginine
• Methionine to Aspartate

Correct Answer: Methionine to Isoleucine

Q16. If a substitution increases local beta‑sheet propensity at an aggregation-prone region, which residue replacement likely contributed to that change?

• Serine to Valine
• Valine to Glycine
• Proline to Glycine
• Alanine to Proline

Correct Answer: Serine to Valine

Q17. In a strategy to stabilize an antibody variable region, introducing a salt bridge typically requires substitution of residues to which complementary pair?

• Glycine and Proline
• Lysine and Glutamate
• Phenylalanine and Tyrosine
• Asparagine and Glutamine

Correct Answer: Lysine and Glutamate

Q18. Which substitution is most useful to block a serine protease cleavage site without drastically altering backbone conformation?

• Serine to Threonine
• Serine to Alanine
• Serine to Proline
• Serine to Aspartate

Correct Answer: Serine to Proline

Q19. Which computational scoring matrix is commonly referenced to evaluate whether an amino acid replacement is evolutionarily conservative?

• Hertzberg matrix
• BLOSUM matrix
• Miller index
• Kd binding matrix

Correct Answer: BLOSUM matrix

Q20. To reduce deamidation and isoaspartate formation at an Asn‑Gly motif, which design change is commonly implemented in a therapeutic protein?

• Replace Gly with Proline
• Replace Asn with Aspartate
• Replace Asn with Gln
• Replace Gly with Valine

Correct Answer: Replace Asn with Gln

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